Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
26 June 2014 to 10 July 2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: There were no deviations (unplanned changes) from the study plan.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2014
Report Date:
2014

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
Principles of method if other than guideline:
None
GLP compliance:
yes (incl. certificate)
Test type:
fixed dose procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Details on test material:
- Appearance/physical state: Clear colourless liquid
- Storage conditions: Room temperature in the dark

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
Five male and five female Wistar strain rats were supplied by Harlan Laboratories UK Ltd., Oxon, UK.
On receipt the animals were randomly allocated to cages. The females were nulliparous and non-pregnant. After an acclimatization period of at least five days, the animals were selected at random and given a number unique within the study by indelible ink-marking on the tail and a number written on a cage card.
At the start of the study the animais weighed at least 200 g, and were eight to twelve weeks of age. The weight variation did not exceed ±20% of the mean weight for each sex.
The animals were housed in suspended solid floor polypropylene cages furnished with woodflakes.
The animals were housed individually during the 24-Hour exposure period and in groups of five, by sex, for the remainder of the study.
Free access to mains drinking water and food was allowed throughout the study. The diet, drinking water and bedding were routinely analyzed and were considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity of the study.

The temperature and relative humidity were set to achieve limits of 19 to 25 °C and 30 to 70 % respectively. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light (06:00 to 18:00) and twelve hours darkness.

The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
The calculated volume of test item, as received, was applied as evenly as possible to an area of shorn skin (approximately 10% of the total body surface area) using a graduated syringe. A piece of surgical gauze was placed over the treatment area and semi occluded with a piece of self adhesive bandage.
The animals were caged individually for the 24-Hour exposure period. Shortly after dosing the dressings were examined to ensure that they were securely in place.

The animals were observed for deaths or overt signs of toxicity 1/2, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days.
Duration of exposure:
After the 24-Hour contact period the bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with arachis oil BP to remove any residual test item. The animals were returned to group housing for the remainder of the study period.
Doses:
Test item at a dose level of 2000 mg/kg.
No. of animals per sex per dose:
a group of five male and five female rats was treated
Control animals:
no
Details on study design:
After removal of the dressings and subsequenty once daily for fourteen days, the test sites were examined for evidence of primary irritation and scored.
Any other skin reactions, if present were also recorded.
Individual body weights were recorded prior to application of the test item on Day 0 and on Days 7 and 14.
At the end of the study the animals were killed by cervical dislocation. All animals were subjected to gross necropsy. This consisted of an extemal examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.
Statistics:
Using the mortality data obtained, an estimate of the acute dermal median lethal dose (LD50) of the test item was made.

Results and discussion

Preliminary study:
None
Effect levels
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths.
Clinical signs:
No signs of systemic toxicity were noted during the observation period.
Body weight:
All animals showed expected gains in body weight over the observation period.
Gross pathology:
No abnormalities were noted at necropsy.
Other findings:
Very slight erythema was noted at the test site of one female two to seven days after dosing. Crust formation and/or glossy skin were noted at the test sites of four females five to seven days after dosing. Small superficial scattered scabs were also noted at the test site of one female three to eight days after dosing.
There were no signs of dermal irritation noted at the test sites of all males and one female.

Any other information on results incl. tables

- Refer to Tables 1 to 5 (attached)

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The acute dermal median lethal dose (LD50) of the test item in the Wistar strain rat was found to be greater than 2000 mg/kg body weight.
Executive summary:

Introduction

The study was performed to OECD Guideline No. 402 and EU Method B.3 to assess the acute dermal toxicity of the test item in the Wistar strain rat.

Methods

A group often animals (five males and five females) was given a single, 24 hour, semi-occluded dermal application of the undiluted test item to intact skin at a dose level of 2000 mg/kg body weight. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy.

Results

Mortality: There were no deaths.

Clinical Observations: There were no signs of systemic toxicity.

Dermal Irritation: Signs of dermal irritation noted at the test sites of four females included very slight erythema, crust formation, glossy skin and small superficial scattered scabs. There were no signs of dermal irritation noted at the test sites of all males and one female.

Body Weight: All animals showed expected gains in body weight.

Necropsy. No abnormalities were noted at necropsy.

Conclusion

The acute dermal median lethal dose (LD50) of the test item in the Wistar strain rat was found to be greater than 2000 mg/kg body weight.